1. The Field of the Invention
The invention relates to treatment of cancer and viral infections and more particularly to therapies using a monoclonal antibody to thymidine kinase.
2. The Background Art
Thymidine kinase (ATP:thymidine-5′ phosphotransferase; EC 2.7.1.21 in the International Union of Biochemistry classification system) is an enzyme that phosphorylates thymidine to thymidine monophosphate (TMP). The commonly used abbreviation of TK will be used herein to denote thymidine kinase in a general sense, where different TK isozymes are not specified particularly.
Thymidine kinase protein has been isolated from many different sources and purified to varying degrees. A variety of different molecular weight thymidine kinases have been reported from human samples, depending on the particular cell and the method of isolation and analysis. In general, thymidine kinase may exist in at least one monomeric form and a variety of multimeric forms.
In humans, there are at least two major isozymes (similar but distinct forms) of thymidine kinase, referred to herein as TK1 and TK2. These isozymes are produced from different genes, are found in different cellular compartments, and differ in their levels and timing of expression during the cell cycle and according to the cell differentiation state. In humans, the TK1 gene is on chromosome 17 in band q21-22 while the TK2 gene is on chromosome 16. A gene for TK1 has been cloned and sequenced.
There are extensive inconsistent reports in the prior art on the properties of mammalian TK1, with diverging results and observations as to the electrophoretic behavior and kinetic properties. Native molecular weights between 45,000 and 200,000 Daltons (or kilo Daltons, kD) have been reported for the native human TK1 from, for example, leukemic cells at 96 kD versus 150-200 kD, human placenta cells at 45 kD versus 92 kD versus 70 kD, lymphocytes at 110 kD, and human breast cancer cells 177 kD.
TK1 has been observed in serum associated with cancerous mammals. However, no prior art studies or papers known to Applicant propose a plausible transport mechanism moving TK1 from its location of origin inside a cell to serum outside the cell. What is needed is an understanding of the transport processes and biological activity of TK1 in order to use this “evidence” of cancerous cell-division activity to develop a therapy useful to mark and treat cancers, viruses, and the like, which hijack cell division structures and chemistry to propagate themselves and infected cell structures.